rs776187492

Variant names:

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_001164508.2(NEB):c.14914T>A(p.Ser4972Thr) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0015 ( 11 hom. )

Failed GnomAD Quality Control

Consequence

NEB
NM_001164508.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.61

Variant links:

Genes affected

NEB (HGNC:7720): (nebulin) This gene encodes nebulin, a giant protein component of the cytoskeletal matrix that coexists with the thick and thin filaments within the sarcomeres of skeletal muscle. In most vertebrates, nebulin accounts for 3 to 4% of the total myofibrillar protein. The encoded protein contains approximately 30-amino acid long modules that can be classified into 7 types and other repeated modules. Protein isoform sizes vary from 600 to 800 kD due to alternative splicing that is tissue-, species-,and developmental stage-specific. Of the 183 exons in the nebulin gene, at least 43 are alternatively spliced, although exons 143 and 144 are not found in the same transcript. Of the several thousand transcript variants predicted for nebulin, the RefSeq Project has decided to create three representative RefSeq records. Mutations in this gene are associated with recessive nemaline myopathy. [provided by RefSeq, Sep 2009]

NEB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010239273).

BP6

Variant 2-151591368-A-T is Benign according to our data. Variant chr2-151591368-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 257748.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-151591368-A-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEB	NM_001164507.2 link	c.14914T>A	p.Ser4972Thr	missense_variant	Exon 96 of 182	ENST00000427231.7	NP_001157979.2
NEB	NM_001164508.2 link	c.14914T>A	p.Ser4972Thr	missense_variant	Exon 96 of 182	ENST00000397345.8	NP_001157980.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NEB	ENST00000397345.8 link	c.14914T>A	p.Ser4972Thr	missense_variant	Exon 96 of 182	5	NM_001164508.2	ENSP00000380505.3	P20929-2
NEB	ENST00000427231.7 link	c.14914T>A	p.Ser4972Thr	missense_variant	Exon 96 of 182	5	NM_001164507.2	ENSP00000416578.2	P20929-3
NEB	ENST00000409198.5 link	c.11602-15014T>A		intron_variant	Intron 78 of 149	5		ENSP00000386259.1	P20929-4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

208

AN:

152152

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00160

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00326

Gnomad SAS

AF:

0.0214

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.000955

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00147

AC:

2048

AN:

1397180

Hom.:

Cov.:

AF XY:

0.00197

AC XY:

1357

AN XY:

689042

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00246

Gnomad4 SAS exome

AF:

0.0192

Gnomad4 FIN exome

AF:

0.000344

Gnomad4 NFE exome

AF:

0.000239

Gnomad4 OTH exome

AF:

0.00223

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00137

AC:

208

AN:

152270

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

125

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00327

Gnomad4 SAS

AF:

0.0214

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00106

Hom.:

ExAC

AF:

0.00262

AC:

185

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Jan 12, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.010

.;T;.;.;.

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.72

T;T;T;.;.

MetaRNN

Benign

0.010

T;T;T;T;T

MetaSVM

Benign

-0.64

PROVEAN

Benign

-0.34

N;.;N;.;.

REVEL

Benign

0.16

Sift

Benign

0.33

T;.;T;.;.

Sift4G

Pathogenic

0.0

D;D;D;D;D

Vest4

0.46

MutPred

0.43

Loss of disorder (P = 0.0986);Loss of disorder (P = 0.0986);Loss of disorder (P = 0.0986);Loss of disorder (P = 0.0986);Loss of disorder (P = 0.0986);

MVP

0.67

MPC

0.21

ClinPred

0.025

GERP RS

3.2

gMVP

0.0052

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over